A rare gift

He was interested in medicine because his father was a doctor. Curiosity about scientific research came from his postgraduate mentors. Born in Liverpool, England, Nicholas Oliver Davidson, M.D., says his father, an anesthesiologist, was a big influence on his decision to go into medicine. Jack Davidson, M.D., worked at one of the teaching hospitals of the University of Liverpool, and he encouraged his son to spend his summers helping out in the hospital, assisting researchers in laboratories there.

Nicholas Davidson attended both college and medical school at Kings College, University of London. But even before earning a medical degree, Davidson, now a professor of medicine and of developmental biology and chief of the Division of Gastroenterology, had his sights set on a career in research.

“Between my third and fourth years of medical school in England, I had an opportunity to come to Chicago and spend a summer doing research,” he says. “That really solidified my interest in wanting to pursue it as a career.”

Mentored in New York

Originally, he had intended to do some postgraduate research in the United States and then return to England, but the opportunities he found in America, combined with personal factors — like meeting his future wife — kept him stateside.

After his medical residency in England, he traveled to New York, where he became a clinical scholar at Rockefeller University. Because Kings College Hospital was a premier liver center, he had a keen interest in liver disease.

“The director of the laboratory at Rockefeller was Dr. E.H. ‘Pete’ Ahrens Jr., who described the original case of primary biliary cirrhosis in a young woman with very high levels of blood cholesterol and cirrhosis of the liver,” Davidson says. “My work at Rockefeller involved clinical research studying hepatic cholesterol metabolism in humans.”

He also met his future wife, Jeanne Most, who was a biostatistician at Rockefeller. The couple will celebrate 30 years of marriage in December.

From Rockefeller, he moved to the then Columbia-Presbyterian Hospital, now New York-Presbyterian/Columbia University Medical Center, for a gastroenterology fellowship. He gives credit to his mentors for helping to plug him into an area of research that was really taking off just as his career was beginning.

“I had terrific mentors,” he says. “At Rockefeller, I had been working on cholesterol metabolism in the liver and became interested in the regulation of cholesterol absorption and bile acid metabolism. At Columbia University, my mentor, Dr. Bob Glickman, was pioneering the study of fat and cholesterol metabolism in the intestine.

“And basically, I was lucky enough to be there with enthusiasm and energy and a desire to learn at a time when the field was exploding,” he says. “I’ve managed to maintain a scientific dialogue between hepatic and intestinal lipid metabolism for most of my career, which has led me in very interesting and unpredictable directions.”

Becoming a mentor

After completing a gastroenterology fellowship, Davidson relocated to the University of Chicago as an assistant professor to set up his own laboratory. After 12 years there, rising through the ranks to professor of medicine, he was recruited to St. Louis and Washington University in 1998 to lead the Division of Gastroenterology.

At both of those stops, he has attempted to do for young scientists what his mentors did for him early in his career. And he has been successful, according to C. Prakash Gyawali, M.D., associate professor of medicine and associate director of the fellowship program in gastroenterology.

“I was the first faculty member Nick hired when he took over the GI division, so we share a special bond,” Gyawali says. “He has been extremely supportive and contributed significantly to my growth in my academic career. He is able to critique trainees on their endoscopic techniques just as easily as he can point out flaws in research studies evaluating genetic influences in lipid metabolism. This is a rare gift, and one that benefits trainees and faculty alike.”

Davidson’s laboratory uses mouse models to study the identity and regulation of genetic pathways involved in lipid metabolism. For example, his lab developed a strain of mice lacking a gene called liver fatty acid binding protein (L-Fabp). Even when these mice eat high-fat diets, they don’t become obese. Davidson says the mice without L-Fabp may provide scientists with tools to help them decouple obesity itself from obesity-related problems.

“We’re interested in genetic regulation of obesity and why high-fat diets tend to induce different responses in terms of weight gain and what genetic components influence that process and affect fat accumulation in the liver and the intestine,” he says. “We’re also interested in the interaction between those genes and growth and development in the intestine, as well as how they influence the pathogenesis of certain cancers.”

Davidson also is credited with identifying and characterizing the molecular machinery responsible for one of the key steps in intestinal fat absorption. His lab cloned an RNA-editing enzyme called apobec-1, which regulates a critically important step in exporting lipids from the intestine. His group has gone on to examine the role of apobec-1 in the regulation of other RNAs, including those involved in the initiation and progression of cancer.

His laboratory concentrates particularly on the genes that regulate cell metabolism in the liver and the intestine, focusing on the mechanisms of gene regulation, primarily at the RNA level, and to examine how changes in certain RNAs influence growth, health and disease in the gut.

He also is very excited about a study involving families with inherited and genetic susceptibility to cancers in the gastrointestinal tract. Washington University has one of the larger registries of familial GI cancers in the country, and working with Alison J. Whelan, M.D., and Deborah C. Rubin, M.D., both professors of medicine, and James W. Fleshman Jr., M.D., professor and chief of colorectal surgery, Davidson is studying families with familial adenomatous polyposis (FAP). The research team hopes to better understand the genetic factors that contribute to the clinical variability seen within families affected by FAP.

Through all of the research efforts, Rubin says fellows and junior faculty are never far from Davidson’s mind.

“He meets with them regularly to assess their progress and deal with their concerns,” she says. “And he has developed a very organized program for mentoring, including establishing senior faculty mentoring committees and creating a lecture series to deal with issues such as how to write a grant, how to run a lab and work/family considerations. His willingness to give so much time and to provide such detailed and extensive feedback is highly unusual and very valuable for those just beginning their careers in science.”

‘Soccer hooligan’

As a Liverpool native, Davidson is aware that the two most famous exports of the city of his birth are the Beatles and soccer hooligans.

“I am a soccer hooligan,” he jokes. “That’s a dominantly imprinted genetic aberration. I’m a die-hard Liverpool fan.”

His television is tuned to the Fox Soccer Channel, and he regularly watches games from the European Champions League with a small group of close friends. This year’s final pitted Spain’s Barcelona club against one of Liverpool’s longtime rivals in the English Premier League, Manchester United. Davidson smiles broadly when recalling the final score: Barcelona 2, Manchester United nothing.

Davidson also has been a coach, supervising his sons, Jeremy and Andrew, as they learned to play soccer when the family lived in Chicago and, for a brief time, here in St. Louis. Recalling that experience elicits an even bigger smile than a Manchester United loss.

He says coaching and playing soccer have provided important life lessons. Aside from the obvious challenges of helping people find ways to play well together and build team spirit, he says it always is a humbling experience to facilitate and encourage personal growth in individuals with different talents and skill sets, and he says these experiences provide some parallels with his position as chief of gastroenterology.

“It has been an enormous privilege to assist in and support the growth and development of our fellows and junior faculty in gastroenterology as they move forward and become leaders in their field,” he says. “That’s what good coaches do.”